Lamin, M. | Search bioRxiv

bioRxiv2026

Detecting DNA methylation patterns suggestive of variable escape from X-chromosome inactivation

The X chromosome is often excluded from studies analyzing associations between traits and DNA methylation. In females, one copy of most genes on the X is inactivated (X-chromosome inactivation; XCI) through DNA methylation of the gene promoter on the inactive X. This leads to challenges in analyzing and interpreting DNA methylation data patterns. Particularly for sex-biased diseases and traits, there may be many loci of interest on the X chromosome, which contains about 5% of the genome. To address the need for appropriate analysis of DNA methylation data on the X chromosome, we develop a statistical approach to infer locus-specific escape from XCI sensitive to phenotype or covariate values. Performance of this method is illustrated by analysis of data from two sex-biased traits: rheumatoid arthritis which is 3-fold more common in females, and recurrent venous thromboembolism which occurs 2.5 times more often in males. Analyses of these two datasets identify new trait-associated loci on the X chromosome, demonstrate the capabilities of the new method for both bisulfite sequencing data and Illumina EPIC data, suggest at least one locus where variable escape may explain a sex-specific disease association, and rule out variable escape as a potential explanation at other loci. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=176 HEIGHT=200 SRC="FIGDIR/small/732395v1_ufig1.gif" ALT="Figure 1"> View larger version (52K): org.highwire.dtl.DTLVardef@108c23aorg.highwire.dtl.DTLVardef@77dc0org.highwire.dtl.DTLVardef@1d105d0org.highwire.dtl.DTLVardef@1d4b543_HPS_FORMAT_FIGEXP M_FIG C_FIG Created with BioRender (bioRender.com)

genomics↗

bioRxiv2024

Genetic diversity and antimicrobial resistance of Campylobacter jejuni isolates from Gambian children under five with moderate-to-severe diarrhoea and healthy Controls

IntroductionCampylobacter is a leading cause of bacterial gastroenteritis globally, but its molecular epidemiology remains poorly understood in sub-Saharan Africa. This study investigates the genotypic population structure of Campylobacter jejuni isolates from children with moderate-to-severe diarrhoea (MSD) and healthy controls in The Gambia. Additionally, we determined the antimicrobial susceptibility levels of the isolates. MethodsAs part of the Global Enteric Multicenter Study (GEMS) in The Gambia, a total of 49 C. jejuni isolates were collected from the stools of children under 5 years old, including 22 with MSD and 27 healthy controls. These isolates were subjected to multilocus sequence typing (MLST) and antimicrobial susceptibility testing using the disc-diffusion method. ResultsThe C. jejuni isolates belonged to 22 sequence types (STs), ten of which were novel. The most common STs were ST-353 (19.1%, 9/47), ST-7784 (12.7%, 6/47), and ST-1038 (10.6%, 5/47). All isolates were fully susceptible to erythromycin, tetracycline, gentamicin and chloramphenicol, with two isolates (4.4%, 2/45) resistant to ciprofloxacin and nalidixic acid. Antimicrobial resistance or intermediate susceptibility to trimethoprim-sulfamethoxazole, cefotaxime and ampicillin was observed in 91.1% (41/45), 90.9% (40/44), and 44.4% (20/45) of the isolates, respectively. There was no strong evidence linking C. jejuni antimicrobial susceptibility or MLST genotype to MSD status. ConclusionThis study provides the first overview of the high genotypic diversity of human C. jejuni isolates in The Gambia and reveals low-level resistance among the isolates to antibiotics commonly used to treat campylobacteriosis. The study contributes to understanding the epidemiology and resistance patterns of C. jejuni in this region.

microbiology↗